The Pathophysiology of Septic Acute Kidney Injury

Grant number: 1050672 | Funding period: 2013 - 2015

Completed

Abstract

Septic shock is a common clinical problem; it is frequently associated with kidney failure that increases mortality. We aim to determine the changes within the kidney that cause it to fail. We will establish whether oxygen levels and blood flow are altered within the kidney, and if blood is shunted through specific blood vessels, reducing flow in critical areas. Importantly, we will determine if clinical treatments used to improve kidney function cause long-term damage by reducing tissue oxygen.

Related publications (26)

Reversal of cerebral ischaemia and hypoxia and of sickness behaviour by megadose sodium ascorbate in ovine Gram-negative sepsis. Response to Br J Anaesth 2026; 136: 781-2.

Clive N May, Mark P Plummer, Yugeesh R Lankadeva

2026-05-01

Reversal of cerebral ischaemia and hypoxia and of sickness behaviour by megadose sodium ascorbate in ovine Gram-negative sepsis

Clive N May, Connie P Ow, Ruslan Pustovit, Darius J Lane, Alemayehu H Jufar, Anton Trask-Marino, Rachel M Peiris, Adam Gunn, Lindsea C Booth, Mark P Plummer, Rinaldo Bellomo, Yugeesh R Lankadeva

2024-08-01

Background: The mechanisms by which megadose sodium ascorbate improves clinical status in experimental sepsis is unclear. We deter..

Continuous bladder urinary oxygen tension as a new tool to monitor medullary oxygenation in the critically ill

RT Hu, YR Lankadeva, F Yanase, EA Osawa, RG Evans, R Bellomo

2022-12-01

Acute kidney injury (AKI) is common in the critically ill. Inadequate renal medullary tissue oxygenation has been linked to its pa..

Targeting oxidative stress in septic acute kidney injury: From theory to practice

CPC Ow, A Trask-Marino, AH Betrie, RG Evans, CN May, YR Lankadeva

2021-09-01

Sepsis is the leading cause of acute kidney injury (AKI) and leads to increased morbidity and mortality in intensive care units. C..

Emerging benefits and drawbacks of α2-adrenoceptor agonists in the management of sepsis and critical illness

YR Lankadeva, Y Shehabi, AM Deane, MP Plummer, R Bellomo, CN May

2021-03-01

Agonists of α<inf>2</inf>-adrenoceptors are increasingly being used for the provision of comfort, sedation and the management of d..

Reversal of the Pathophysiological Responses to Gram-Negative Sepsis by Megadose Vitamin C

YR Lankadeva, RM Peiris, N Okazaki, IE Birchall, A Trask-Marino, A Dornom, TAM Vale, RG Evans, F Yanase, R Bellomo, CN May

2021-02-01

Objectives: Oxidative stress appears to initiate organ failure in sepsis, justifying treatment with antioxidants such as vitamin C..

Systemic haemodynamic, renal perfusion and renal oxygenation responses to changes in inspired oxygen fraction during total intravenous or volatile anaesthesia

N Iguchi, J Kosaka, Y Iguchi, RG Evans, R Bellomo, CN May, YR Lankadeva

2020-08-01

Background: Anaesthesia-induced changes in renal perfusion are dependent on the choice of anaesthetic agent. However, the effects ..

Dexmedetomidine reduces norepinephrine requirements and preserves renal oxygenation and function in ovine septic acute kidney injury

YR Lankadeva, S Ma, N Iguchi, RG Evans, SG Hood, DGS Farmer, SR Bailey, R Bellomo, CN May

2019-11-01

Norepinephrine exacerbates renal medullary hypoxia in experimental septic acute kidney injury. Here we examined whether dexmedetom..

Renal Medullary Hypoxia: A New Therapeutic Target for Septic Acute Kidney Injury?

YR Lankadeva, N Okazaki, RG Evans, R Bellomo, CN May

2019-11-01

Summary: Renal tissue hypoxia has been implicated as a critical mediatory factor in multiple forms of acute kidney injury (AKI), i..

Furosemide reverses medullary tissue hypoxia in ovine septic acute kidney injury

N Iguchi, YR Lankadeva, TA Mori, EA Osawa, SL Cutuli, RG Evans, R Bellomo, CN May

2019-08-01

In experimental sepsis, the rapid development of renal medullary hypoxia precedes the development of acute kidney injury (AKI) and..

Renal perfusion, oxygenation, and sympathetic nerve activity during volatile or intravenous general anaesthesia in sheep

N Iguchi, J Kosaka, LC Booth, Y Iguchi, RG Evans, R Bellomo, CN May, YR Lankadeva

2019-03-01

Background: Global and intra-renal perfusion and oxygenation may be affected by the choice of anaesthetic. We compared the effects..

Factors that confound the prediction of renal medullary oxygenation and risk of acute kidney injury from measurement of bladder urine oxygen tension

JP Ngo, YR Lankadeva, MZL Zhu, A Martin, M Kanki, AD Cochrane, JA Smith, AG Thrift, CN May, RG Evans

2019-01-01

Aim: Urinary oxygen tension (uPO<inf>2</inf>) may provide an estimate of renal medullary PO<inf>2</inf> (mPO<inf>2</inf>) and thus..

Alterations in regional kidney oxygenation during expansion of extracellular fluid volume in conscious healthy sheep

YR Lankadeva, RG Evans, J Kosaka, LC Booth, N Iguchi, R Bellomo, CN May

2018-12-01

Expansion of extracellular fluid volume with crystalloid solutions is a common medical intervention, but its effects on renal cort..

Renal haemodynamics and oxygenation during and after cardiac surgery and cardiopulmonary bypass

RG Evans, YR Lankadeva, AD Cochrane, B Marino, N Iguchi, MZL Zhu, SG Hood, JA Smith, R Bellomo, BS Gardiner, CJ Lee, DW Smith, CN May

2018-03-01

Acute kidney injury (AKI) is a common complication following cardiac surgery performed on cardiopulmonary bypass (CPB) and has imp..

An ovine model for studying the pathophysiology of septic acute kidney injury

YR Lankadeva, J Kosaka, RG Evans, CN May

2018-01-01

The development of acute kidney injury (AKI) is both a significant and independent prognostic factor of mortality in patients with..

Urinary Oxygenation as a Surrogate Measure of Medullary Oxygenation during Angiotensin II Therapy in Septic Acute Kidney Injury

YR Lankadeva, J Kosaka, RG Evans, R Bellomo, CN May

2018-01-01

Objectives: Angiotensin II is an emerging therapy for septic acute kidney injury, but it is unknown if its vasoconstrictor action ..

Intrarenal and urinary oxygenation during norepinephrine resuscitation in ovine septic acute kidney injury

YR Lankadeva, J Kosaka, RG Evans, SR Bailey, R Bellomo, CN May

2016-07-01

Norepinephrine is the principal vasopressor used to restore blood pressure in sepsis, but its effects on intrarenal oxygenation ar..

Intrarenal and urinary oxygenation during norepinephrine resuscitation in ovine septic acute kidney injury

Yugeesh R Lankadeva, Junko Kosaka, Roger G Evans, Simon R Bailey, Rinaldo Bellomo, Clive N May

2016-07-01

Intra-renal and Urinary Oxygenation during Resuscitation with Norepinephrine and Angiotensin II in Ovine Acute Kidney Injury

Yugeesh Ryan Lankadeva, Junko Kosaka, Roger G Evans, Rinaldo Bellomo, Clive N May

2016-04-01

<jats:sec> <jats:title>Background and Aims</jats:title> <jats:p> Acu..

Hypoxia as a Biomarker of Kidney Disease

Roger G Evans, Julian A Smith, Bruce S Gardiner, David W Smith, Amanda G Thrift, Clive N May, Yugeesh R Lankadeeva, Andrew D Cochrane

2016-01-01

All established (e.g., serum creatinine, albuminuria) and emerging (e.g., neutrophil gelatinase-associated lipocalin, cystatin C) ..

Cortical and medullary tissue perfusion and oxygenation in experimental septic acute kidney injury

P Calzavacca, RG Evans, M Bailey, R Bellomo, CN May

2015-10-01

Objectives: To determine whether there is a decrease in renal cortical or medullary perfusion and oxygenation in a conscious large..

Clonidine restores pressor responsiveness to phenylephrine and angiotensin II in ovine sepsis

YR Lankadeva, LC Booth, J Kosaka, RG Evans, L Quintin, R Bellomo, CN May

2015-07-21

Objectives: In sepsis, prolonged, sympathetic overstimulation may lead to vasopressor-refractory hypotension. We therefore examine..

Long-term measurement of renal cortical and medullary tissue oxygenation and perfusion in unanesthetized sheep

P Calzavacca, RG Evans, M Bailey, YR Lankadeva, R Bellomo, CN May

2015-05-15

The role of renal cortical and medullary hypoxia in the development of acute kidney injury is controversial, partly due to a lack ..

Hypoxia as a Biomarker of Kidney Disease

Roger G Evans, Julian A Smith, Bruce S Gardiner, David W Smith, Amanda G Thrift, Clive N May, Yugeesh R Lankadeeva, Andrew D Cochrane

2015-01-01

All established (e.g., serum creatinine, albuminuria) and emerging (e.g., neutrophil gelatinase-associated lipocalin, cystatin C) ..

Variable responses of regional renal oxygenation and perfusion to vasoactive agents in awake sheep

P Calzavacca, RG Evans, M Bailey, R Bellomo, CN May

2015-01-01

Vasoactive agents are used in critical care to optimize circulatory function, but their effects on renal tissue oxygenation in the..

Effects of renal denervation on regional hemodynamics and kidney function in experimental hyperdynamic sepsis

P Calzavacca, M Bailey, E Velkoska, LM Burrell, R Ramchandra, R Bellomo, CN May

2014-01-01

OBJECTIVE: To determine the influence of the renal sympathetic nerves on the pathogenesis of septic acute kidney injury. DESIGN: I..

University of Melbourne Researchers

Clive May